All-Cause Mortality Risk With Adjuvant vs Early Salvage Radiotherapy After Radical Prostatectomy

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In a retrospective cohort study reported in the Journal of Clinical Oncology, Tilki et al found that adjuvant radiotherapy was associated with reduced risk for all-cause mortality vs early salvage radiotherapy among men at high risk for disease recurrence following radical prostatectomy.

As stated by the investigators, “Three randomized trials and an associated meta-analysis found no difference in progression-free survival when comparing adjuvant with early salvage radiotherapy, which can cause many physicians to not offer adjuvant radiotherapy, irrespective of the pathologic findings at radical prostatectomy. We provide evidence to support that adjuvant compared with early salvage radiotherapy may lower the risk of death in men with adverse pathology at radical prostatectomy.” 

Study Details

The study cohort consisted of 26,118 men with pT2-4N0 or N1M0 prostate cancer consecutively treated between June 1989 and July 2016 with radical prostatectomy and pelvic lymph node assessment and then followed for potential treatment with adjuvant or early salvage radiotherapy at three German and two U.S. centers.

Follow-up started on the date of radical prostatectomy; the database was last updated in October 2020.

The primary outcome measure was risk of all-cause mortality risk in men with adverse pathology, defined as positive pelvic lymph nodes (pN1) or prostatectomy Gleason score 8 to 10 and disease extending beyond the prostate (pT3/4). Analyses included use of a treatment propensity score to minimize potential treatment selection bias in estimating the causal association of adjuvant vs early salvage radiotherapy on all-cause mortality risk. Analyses were performed to assess the effect of different definitions of adverse pathology on all-cause mortality risk—eg, exclusion of pN1 disease and exclusion of early salvage radiotherapy patients with persistent postsurgery prostate-specific antigen level. Multivariate analyses were adjusted for age at radical prostatectomy, prostate cancer prognostic factors, study site, and time-dependent use of postprostatectomy androgen-deprivation therapy.

Adjuvant radiation therapy should be considered in men with pN1 or [prostatectomy] Gleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in all-cause mortality risk exists.
— Tilki et al

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Key Findings

Median follow-up was 8.16 years (interquartile range = 6.00­–12.10 years). Among the 26,118 patients, 2,104 (8.06%) died, including 539 (25.6%) from prostate cancer.

Adverse pathology at radical prostatectomy was identified in 2,424 patients when those with pN1 disease were included and in 933 when those with pN1 were excluded (pN0 disease). Among the 2,424 patients, 428 received adjuvant radiotherapy, 965 received no radiotherapy, and 1,031 received early salvage radiotherapy. Among the 933, 109 received adjuvant radiotherapy, 379 received no radiotherapy, and 445 received early salvage radiotherapy.

On multivariate analysis, compared with early salvage radiotherapy, men receiving adjuvant radiotherapy had significantly lower risk of all-cause mortality both when patients with pN1 disease were included (adjusted hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.41–0.89, P =.01) and when those with pN1 disease were excluded (HR = 0.31, 95% CI = 0.12–0.78, P = .01). Compared with early salvage radiotherapy, no significant differences in all-cause mortality risk were observed among patients receiving no radiotherapy when pN1 disease was included (HR = 1.09, 95% CI = 0.88–1.36, P = .42) or excluded (HR = 1.14, 95% CI = 0.83–1.57, P = .42).

In analysis excluding patients in the early salvage radiotherapy group with a persistent postoperative prostate-specific antigen level, significantly reduced all-cause mortality risk with adjuvant radiotherapy was maintained both when pN1 disease was included (total n = 2,106; HR = 0.66, 95% CI = 0.44–0.99, P = .04) and excluded (total n = 826; HR = 0.33, 95% CI = 0.13–0.85, P = .02). 

Among 23,694 patients without adverse pathology at radical prostatectomy, 391 received adjuvant radiotherapy, 19,733 received no radiotherapy, and 3,570 received early salvage radiotherapy. Compared with early salvage radiotherapy, no significant difference in risk for all-cause mortality was observed among men receiving adjuvant radiotherapy (HR = 0.78, 95% CI = 0.50–1.22, P = .28) or no radiotherapy (HR = 1.07, 95% CI = 0.93–1.23, P = .33).

The investigators concluded, “Adjuvant radiation therapy should be considered in men with pN1 or [prostatectomy] Gleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in all-cause mortality risk exists.”

Anthony V. D’Amico, MD, PhD, of Brigham and Women’s Hospital and Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit

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